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Antiretroviral therapy may convey metabolic risks.

BOSTON -- Long-term exposure to antiretroviral therapy appears to convey substantial metabolic risk to adolescents and young adults with HIV infection, according to a National Institutes of Health study.

In a cross-sectional investigation of 40 HIV-infected patients aged 11-27 years who acquired HIV in infancy or childhood and had been exposed to antiretroviral therapy (ART), a majority of study participants had impaired glucose tolerance and other metabolic abnormalities, said Dr. Colleen M. Hadigan of the National Institute of Allergy and Infectious Diseases and her colleagues.

While the medical literature is replete with studies linking such metabolic complications as dyslipidemia, lipodystrophy, and insulin resistance to long-term ART in HIV-infected adults, the pediatric literature is relatively sparse, and comprehensive reviews of metabolic consequences of ART in children are rare, Dr. Hadigan reported at the 15th Conference on Retroviruses and Opportunistic Infections.

The current study was designed to characterize the extent of metabolic abnormalities in a cohort of adolescents who acquired HIV infection perinatally or in childhood, she said.

All study subjects were ART experienced, with a mean treatment duration of 14 years, and all had current or past protease inhibitor and stavudine exposure. At the time of the investigation, 88% of the patients were receiving a protease inhibitor. At enrollment, approximately half of the patients had an HIV RNA of less than 50 copies/mL; the mean CD4 count was 665.

According to the study protocol, all of the subjects completed oral glucose tolerance testing and fasting insulin and lipid studies, and all underwent anthropometric assessments including whole body dual-energy x-ray absorptiometry (DXA) scans.

An analysis of the results showed impaired glucose tolerance in 20% of the subjects. The mean fasting insulin level for the group was 18 IU/mL, the mean glucose level was 86 mg/dL, and the mean homeostatic model for assessment of insulin resistance (HOMA) was 3.9, Dr. Hadigan reported at the conference, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Approximately 38% of the subjects had a HOMA value greater than 4.0, and thus met the criteria for insulin resistance, Dr. Hadigan said. In addition, 50% had elevated triglyceride levels (greater than 150 mg/dL), 53% had low levels of HDL cholesterol (less than 50 mg/dL for females and less than 40 mg/dL for males), and 24% had an elevated total cholesterol level (greater than 200 mg/dL).

With respect to body mass index (BMI) and body fat, the mean BMI was 22 kg/[m.sup.2], the mean waist-to-hip ratio was 0.92, and the mean percentage of body fat by DXA was 20.

Approximately 15% of the subjects were overweight, with a BMI greater than 25 kg/[m.sup.2], and one patient was obese, with a BMI greater than 30 kg/[m.sup.2]. Similarly, 16% of the subjects had a waist-to-hip ratio greater than 1.00.

Of interest, Dr. Hadigan noted, was the fact that insulin resistance by HOMA was significantly positively correlated with waist-to-hip ratio in this mostly nonobese population.

Although none of the subjects had type 2 diabetes, the results suggest that long-term exposure to ART may substantially increase their risk for that outcome as well as for cardiovascular disease, Dr. Hadigan warned.

As such, "these findings warrant careful monitoring in this population, as well as further research," she added.


New England Bureau
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Title Annotation:Infectious Diseases
Author:Mahoney, Diana
Publication:Internal Medicine News
Geographic Code:1USA
Date:Mar 15, 2008
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